Should We Screen All Patients With Hepatitis B for Hepatitis Delta?

Hepatitis delta virus (HDV) is the most severe form of viral hepatitis, with higher rates of hepatic decompensation, hepatocellular carcinoma, and liver transplantation in people with HDV infection compared with those monoinfected with hepatitis B virus (HBV) or hepatitis C virus. It has remained challenging to determine the prevalence of HDV in the United States and worldwide. This is due in part to the wide geographic distribution of HDV, accompanied by variable and inconsistent screening recommendations and implementation strategies to help identify undiagnosed cases. Current prevalence estimates for HDV range from 4.5% to 16.4%. 

Hepatitis Delta Screening
At the American Association for the Study of Liver (AASLD) 2021 meeting, several presentations highlighted the challenges we face in improving both screening rates and linkage to care for HDV.

Palom and colleagues in Barcelona, Spain, assessed rates of HDV screening in 4386 patients who had undergone hepatitis B testing at an academic center and 17 primary care clinics between 2015 and 2021. I think their study highlights the challenges that we face in trying to identify the large pool of undiagnosed individuals with chronic HDV infection. They reported that 8.2% of patients were screened for anti-HDV antibodies, with 10.3% of these tests being positive, for an overall prevalence of 0.8% anti-HDV positivity in the cohort. This screening rate was observed in the context of the universal HDV screening recommendation in the European Association for the Study of the Liver (EASL) Hepatitis B Guideline.

In the Barcelona cohort, 7.5% of patients tested for HDV were tested before the 2017 EASL guideline publication. By contrast, in 2018 and later, there was an improvement in the proportion of patients tested (9.4%). Although two thirds of the hepatitis B surface antigen (HBsAg) testing occurred in the primary care setting, anti-HDV testing was predominantly ordered by healthcare professionals practicing in an academic setting: 78% of screening tests were performed there vs 22% of screening tests being carried out in primary care.

HDV RNA testing confirmed viremia in 84%, with more than 80% having active HDV RNA viremia present. Not surprisingly, most individuals testing positive were from migrant populations, with 30% having advanced liver disease.

Gaps in the Care Cascade
In the quest to eliminate viral hepatitis, the largest gap in the cascade of care has been diagnosis and linkage to care in those with chronic viral hepatitis. Strategies for HDV screening include risk-based screening (recommended by AASLD) and universal screening of all patients with HBV infection (recommended by the recent EASL and Asian-Pacific Association for the Study of the Liver guidance). Even though data from 1672 individuals in the Barcelona study were collected after universal HDV screening was recommended in the guidelines, the overall rate of screening was unacceptably low, with higher rates in the academic practice compared with the community practice setting. Clearly, more education, both for our specialists and our primary care healthcare professionals, will be required to improve HDV screening and diagnosis rates even when universal screening is recommended.

Regarding hepatitis C virus (HCV) screening in the United States, we have evolved from risk-based screening to adding birth cohort screening and now to universal screening. There have been recent modifications to hepatitis B virus (HBV) screening guidelines as well. Universal screening for HDV in those infected with HBV may be the most effective policy to reduce the number of undiagnosed individuals with chronic HDV infection. Reflex testing policies for HDV with anti-HDV and HDV RNA when testing for the presence of HBsAg may also be an effective measure to improve screening rates and would be similar to the reflex testing strategy now employed with samples from individuals who test positive with the HCV antibody test that are automatically tested for HCV RNA.

Currently, bulevirtide is the single, conditionally approved therapy in the European Union for HDV, and it was also recently granted Orphan Drug status in the United States. With other promising therapies currently in phase III trials, healthcare professionals will soon have medications available to treat those with chronic HDV infection. Given the severity of this disorder, it is critical that we identify—and link to care—this population that has remained elusive thus far.

Your Thoughts?
Do you practice universal HDV screening of all patients with HBV? Join the discussion by posting a comment. For more details on this and other key viral hepatitis issues from AASLD 2021, review more CCO Conference Coverage, including video and audio recaps with expert faculty.